Human spinal cord injuries (SCIs) affect multiple cell types and after the initial injury, a self-propagating cascade of cellular and biochemical mechanisms lead to additional tissue loss that exacerbates the SCI. The zebrafish central nervous system (CNS) shares many organizational, cellular and molecular pathways with mammals; however, functional regeneration occurs in zebrafish even after complete transection of the spinal cord. Our understanding of how the CNS of zebrafish responds to injury and subsequently regenerates remains incomplete. Our long-term goal is to advance our understanding of the cellular response to neural injury and subsequent process of regeneration using optogenetic tools and zebrafish models. The scientific aims of this research plan are to: (1) identify the cellular events that occur after different types of injury and (2) determine changes in the bioelectric network as the basis for locomotor recovery. This project will establish a framework to utilize the zebrafish larvae as a model for studies in neural injury and neurodegeneration. Upon completion, the proposed research is expected to provide a more complete picture of the biological basis for locomotor recovery and provide new therapeutic intervention points.